Hydrazine → Oxadiazole

Participants

Reaction Steps

3-(phenoxy)-4,5-dihydroisoxazole I-224a and I-224b were prepared in 3 steps according to the following procedures: 3-fluoro-5-hydroxybenzoic acid methyl ester is reacted with racemic bromoisoxazole I-14 using Method 5. The resulting methyl ester (1.0 equiv) is dissolved in methanol (0.08 M) after which hydrazine (50 equiv, 50% by weight in water) is added and the reaction is allowed to stir for 14 h. The reaction mixture is then concentrated under vacuum and used directly in the next step. Triethylorthoacetate (8.0 equiv) is added and the reaction is sealed and heated to reflux for 14 h. The reaction is then transferred to a separatory funnel with excess ethyl acetate and water. The organic layer was washed water and brine, drive over sodium sulfate and concentrated under vacuum to provide crude material which was purified using flash silica gel chromatography (gradient ethyl acetate/hexanes) to provide the desired racemic oxadiazole I-224. These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M+H]+=424.5 m/z. Activity: A

Provenance & Evidence